Antifungal Efficacy of Gallic Acid Extracted From Pomegranate Peel Against Trichophyton rubrum: In Vitro Case Study

Objectives: Trichophyton rubrum is one of the main pathogens causing superficial dermatophytosis, producing symptoms such as skin itching and pain, which seriously affects the quality of life of patients. Pomegranate peel extract is rich in gallic acid (GA), which has been reported to have biological effects including antifungal activity. However, the morphological and molecular mechanisms underlying the effects of GA on T rubrum are not well understood. The objectives of this study were to determine the antifungal efficacy of GA extracted from pomegranate peel against T rubrum in vitro, and to explore the underlying molecular mechanisms. Methods: The effects of 0-, 0.5-, and 1 mg/mL GA in pomegranate peel extract on T rubrum was investigated by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Transmission electron microscopy (TEM) was used to analyze the ultrastructure of T. rubrum, and transcriptome sequencing was used to analyze the enrichment pathway of differentially expressed genes. The identification of biosynthesis-related and key genes in the pathways involved using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) technology. Terbinafine hydrochloride (TERB) as a positive control group. Results: Pomegranate peel extract has a GA content of 1.0 mg/mL. Compared with untreated group, following treatment with 1.0 mg/mL GA content is rich in pomegranate peel extract, and the microstructure of T rubrum is destroyed. TEM results show that the number of lipid droplets in T rubrum was significantly increased, mitochondrial vacuoles degenerated, the serosa were damaged, and the boundary of thallus was unclear. In addition, 1 mg/mL GA can significantly inhibit T rubrum proliferation, and its inhibition ability is better than TERB. Transcriptomics results show that GA can change the gene expression profile of T rubrum, specifically: The biosynthesis was blocked, drug resistance was weakened, the transport of ATP-binding cassette (ABC) drugs transporter was increased, and the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited. Conclusions: Pomegranate peel extract is rich in GA, which strongly inhibited the growth of T rubrum and reduced its drug resistance. This extract is a promising natural antifungal agent for clinical use.